Mechanisms which control the frequency distribution of polyribosome-associated messenger RNA sequences will be studied using two closely related clones of AKR mouse embryo cells in culture. Kinetically fractionated cDNA probes have been prepared to poly(A)-containing mRNA sequences which differ by two orders of magnitude in their mean intracellular frequency in AKR clone 2B cells. In addition specific probes have been prepared to endogenous AKR-murine leukemia virus related RNA and to alpha and beta globin chain RNA. MuLV-related RNA transcripts are present in low abundance (approximately 30 molecules/cell) in clone 2B cells and in high abundance (approximately 5000 molecules/cell) in a derivative clone. Neither alpha or beta globin gene transcripts are detectable in either clone at levels of sensitivity corresponding to much less than 1 molecule/cell. Experiments are proposed to investigate the nuclease sensitivity and rate of transcription in isolated nuclei of these various gene sequences to determine if transcriptional controls are the major determinant of mRNA frequency in these cells. These experiments will be complemented by determination of the effect of inhibition of gene transcription on the mRNA frequency distribution in vivo and by analyses of nuclear poly(A)-containing RNA sequences which have no apparent counterpart in steady-state polysomal mRNA.